Michaelis, S

Susan Michaelis, Ph.D.Image

Professor of Cell Biology

Contact Information

Room 104, Biophysics Building
410-955-8286; 410-955-7274
410-955-4129 (Fax)
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Research Interests

The overall goal of our research is to dissect fundamental cellular processes relevant to human health and disease, using yeast and mammalian cell biology, biochemistry, and high-throughput genomic approaches. One project in the laboratory focuses on a rare premature aging disorder, Hutchinson-Gilford progeria syndrome (HGPS), which results from a mutation in the gene (LMNA) encoding the nuclear scaffold protein lamin A.  Children with HGPS exhibit profound characteristic of aging, including hair loss, skin and bone defects, and heart disease.  The mutant form of lamin A in HGPS patient cells is persistently modified by the lipid farnesyl (an aberrant situation, since normally a proteolytic cleavage removes the farnesylated C-terminal tail of lamin A during biogenesis).  Excitingly, we have found that a particular class of anti-cancer drugs called the farnesyl transferase inhibitors (FTIs) can dramatically block the nuclear abnormalities characteristic of HGPS fibroblasts and thus may be useful to treat HGPS.  We are currently examining the basic cell biology of lamin A processing, molecular mechanisms of lamin A toxicity in HGPS, and the link between HGPS and normal aging.


Another project in our laboratory focuses on ER quality control (ERQC), a process which ensures that misfolded secretory and membrane proteins, such as the mutant cystic fibrosis channel protein, are retained in the endoplasmic reticulum and subsequently undergo degradation by the ubiquitin-proteasome system.  Our goal is to identify the core cellular machinery that mediates ERQC.  To do so, we are using misfolded proteins as “bait” in a variety of genome-wide yeast screens designed to uncover the eukaryotic ERQC machinery.  Ultimately, a detailed understanding of the cellular players that mediate this process will facilitate development of treatments for ERQC-based diseases such as cystic fibrosis.

Selected Publications

  • Paumi, C. M., Menendez, J., Arnoldo, A, Engels, K, Iyer, K. R., Thaminy, S, Georgiev, O., Barral Y., Michaelis, S, and Stagljar, I. (2007) Mapping Protein-Protein Interactions for the Yeast ABC Transporter Ycf1p by Integrated Split-Ubiquitin Membrane Yeast Two-Hybrid (iMYTH) Analysis.  Molecular Cell 26: 15-25.
  • Huyer, G., Kistler, A., Nouvet, F. J., George, C., Boyle, M. L., and Michaelis, S.  (2006) Saccharomyces cerevisiae a-factor mutants reveal residues critical for processing, activity, and export.  Eukaryotic Cell 5: 1560-1570.
  • Gelb, M. H., Brunsveld, L., Hrycyna, C. A., Michaelis, S., Tamanoi, F., Van Voorhis, W. C., and Waldmann, H. (2006) Therapeutic intervention based on protein prenylation and associated modifications. Nature Chemical Biology 2:518-528.
  • Mallampalli, M. P., Huyer, G., Bendale, P., Gelb, M. H., and Michaelis, S. (2005) Inhibiting Farnesylation Reverses the Nuclear Morphology Defect in a HeLa Cell Model for Hutchinson-Gilford Progeria Syndrome, Proc Natl. Acad Sci. USA 102:14416-14421.
  • Young, S. G. Fong, L., and Michaelis, S.  (2005) Prelamin A, Zmpste24, misshapen cell nuclei, and progeria- new evidence suggesting that protein farnesylation could be important for disease pathogenesis.  Journal of Lipid Research 46:2531-2558.
  • Anderson, J. L., Frase, H., Michaelis, S., and Hrycyna, C. A.  (2005)  Purification, functional reconstitution and characterization of the Saccharomyces cerevisiae isoprenylcysteine carboxyl methyltransferase Ste14p. J. Biol. Chem. 280:7336-7345.
  • Huyer, G., Piluek, W. F., Fansler, Z., Kreft, S. K., Hochstrasser, M, Brodsky, J. L. and Michaelis, S.  (2004) Distinct machinery is required in Saccharomyces cerevisiae for the endoplasmic reticulum-associated degradation of a multispanning membrane protein and a soluble lumenal protein. J. Biol. Chem.  279:38369-38378.
  • Huyer, G. ,  Longsworth G. L., Mason, D. L., Mallampalli, M. P. McCaffery, J. M., Wright, R.. L., and Michaelis, S. (2004) A novel quality control subcompartment in Saccharomyces cerevisiae: The endoplasmic reticulum-associated compartment (ERAC), Mol. Biol. Cell 15: 908-921.
 
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